Natural peptides have an important signalling function and coordinate many biochemical processes. Because of this, peptides have become indisputably promising active ingredients, particularly in the cosmetics industry where compounds are continually being sought able to beautify the skin and appendages, i.e. able to improve its general state.
There are many ways in cosmetics of improving the general state of the skin and appendages, in particular enhancing or restoring brightness, moisturising, pigmenting or depigmenting, protecting against harmful external factors such as UV rays or the cold, soothing irritation, redness and acne, reducing oedema (such as bags under the eyes), reducing dark circles, signs of ageing such as wrinkles and fine lines, pigmentation, restoring suppleness and elasticity, treating hair loss, acting on adipose tissue, providing volume and density, improving texture, helping healing, and promoting the growth and quality of the skin appendages, etc.
The action mechanisms of peptides are not always known. Results may be obtained with peptides acting, for example, on the skin's extracellular matrix, particularly by promoting the synthesis of molecules, by preventing their degradation or by acting on receptors. The same peptide sometimes has several simultaneous cosmetic effects.
KXK peptides (lysine-AA-lysine) have been proposed as TGF-beta growth factor activators thereby enabling the synthesis of collagen in the skin extracellular matrix. The peptide proposed in document FR2810323 (Shiseido) is elaidyl-KFK, in which the AA amino acid is phenylalanine.
In document EP1625150 (Pentapharm), the inventors describe elaidyl-KFK as being insufficiently active to stimulate collagen synthesis and propose to alter the lysine side chains, for example the length of the aminated alkyl chains or to introduce specific side chains (functionalised) or to use a central amino acid AA with a hydrocarbon chain possibly substituted by a hydroxyl group. Amongst the examples given, Pal-KVK (where Pal is a palmitoyl lipophilic chain), Pal-KAK or Pal-KSK can be found in the application.
Actually these peptides have been found to be relatively ineffective particularly at the concentrations of a few ppm usually used in cosmetics.
WO 99/12968 and WO 00/42071 disclose peptides, variants, derivatives and analogs and their use in therapeutic methods to inhibit or augment an inflammatory response. Tripeptides KXK, with X one of the twenty naturally occurring amino acids are listed, some of them were tested and being TGF-beta activators and/or chemokine antagonists.
The purpose of the present invention is to propose other peptidic compounds, in particular of the KXK type, for the cosmetic and dermopharmaceutic fields, that are able to improve the general state of the skin and its appendages. In addition, the invention aims to propose peptidic compounds sufficiently effective to be used at low proportions of few ppm.